Shih-Yuan Liu

Medium-sized cyclic ethers are present in many natural products and therapeutic agents. Herein, we describe a mild catalytic method for the synthesis of 6- to 8-membered oxacycles by endo-selective hydroalkoxylation of enynols and enynediols. The utility of this method is demonstrated through the total synthesis of (±)-corypsoriol D and E. Experimental and computational mechanistic studies revealed an oxidative syn-outer-sphere proton transfer mechanism, followed by a rate-determining reductive elimination via nucleophilic attack of the alkoxide on the resulting Pd-π-allyl.

Cyclobutane β ‐amino alcohols are valuable structural motifs, yet their development has lagged behind that of five‐ and six‐membered analogs due to limited synthetic accessibility. In this work, we report a general and modular strategy for the synthesis of diversely substituted cyclobutane β ‐amino alcohols. The electronic structure of 1,2‐azaborines is leveraged to achieve regioselective mono‐ and difunctionalization at all four carbon positions. The installed functionalities are subsequently translated into cyclobutane β ‐amino alcohol frameworks through a tandem photoisomerization–hydrogenation–oxidation sequence. This strategy provides access to eight distinct substitution patterns with high levels of modularity and diastereoselectivity.

Cyclobutane β ‐amino alcohols are valuable structural motifs, yet their development has lagged behind that of five‐ and six‐membered analogs due to limited synthetic accessibility. In this work, we report a general and modular strategy for the synthesis of diversely substituted cyclobutane β ‐amino alcohols. The electronic structure of 1,2‐azaborines is leveraged to achieve regioselective mono‐ and difunctionalization at all four carbon positions. The installed functionalities are subsequently translated into cyclobutane β ‐amino alcohol frameworks through a tandem photoisomerization–hydrogenation–oxidation sequence. This strategy provides access to eight distinct substitution patterns with high levels of modularity and diastereoselectivity.

The synthesis of N-trifluoromethyl 1,4-azaborine-based phosphine ligands (FinnPhos) is described. X-ray diffraction analysis of FinnPhos L1-CF3 and its N-methyl analogue reveals a stronger contribution of the neutral resonance form to the structure of the 1,4-azaborine ring. Density functional theory (DFT) calculations predict the FinnPhos to exhibit a unique η³-C,C,B coordination mode to Pd(0). We demonstrate that the N-trifluoromethyl ligand provides superior reactivity to its N-methyl and carbonaceous analogues in the Au-catalyzed cycloisomerization of 1,6-enynes.

Carbon-based benzvalene undergoes diverse rearrangements upon exposure to external stimuli. In this report, we investigate the thermal and metal-catalyzed rearomatization pathways of BN-benzvalene, a boron-nitrogen-containing valence isomer of benzene. Depending on the choice of metal catalyst, these transformations selectively yield either C5- or C3-functionalized 1,2-azaborines. The C5-isomer formation serves as a proof of concept for a new molecular photoswitch system, while the C3-isomer formation represents the functional group transposition on the 1,2-azaborine scaffold. Mechanistic investigations, such as deuterium labeling studies and DFT calculations, suggest distinct operative pathways for the generation of each isomer.

A photochemical positional isomerization approach for converting readily accessible C5-aryl-1,2-azaborines into their C4-aryl counterparts via a BN-benzvalene intermediate is described. The oxidative radical cation pathway from BN-benzvalene to the C4-aryl products is supported by deuterium labeling experiments, transient absorption (TA) spectroscopy, and DFT calculations. The reaction's utility is demonstrated by providing the first general method to C4,C5-difunctionalized 1,2-azaborines and the regioselective synthesis of hexa-substituted derivatives.

Medium-sized cyclic ethers are present in many natural products and therapeutic agents. Herein we describe a mild catalytic method for the synthesis of 6-to-8-membered oxacycles by endo-selective hydroalkoxylation of enynols and enynediols. The utility of this method is demonstrated through the total synthesis of (±)-Corypsoriol D and E. Experimental and computational mechanistic studies re- vealed a syn-outer-sphere proton transfer mechanism involving a rate-determining reductive elimination.

The first solution-phase synthesis and reactivity of a nitrilium-type N-hetaryne are described. The 1,2-azaborine-derived 1,6-BN-aryne 2 exhibits [4 + 2], [3 + 2], and [2 + 2] cycloadditions and electrophilic aromatic substitution (EAS) reactivity. The observed regio- and diastereoselectivities of the cycloaddition and EAS products are consistent with a polarized aryne/nitrilium species. The free 1,6-BN-aryne 2 was isolated and characterized under matrix isolation conditions. A Lewis structure description where the 1,6-BN-aryne 2 resonates between two limiting (ketenimine (dominant) vs nitrilium) forms is consistent with DFT calculations. New 1,2-azaborine structures that are functionalized at the C6- and N-positions, including highly strained derivatives that were previously not accessible, can now be accessed using 1,6-BN-aryne 2 as a versatile synthetic building block.

We describe herein an iridium‐catalyzed highly diastereo‐ and enantioselective hydrogenation of 1,2‐azaborines to access δ‐aminoboronic esters of potential biological importance. This method represents the first enantioselective hydrogenation of a boron‐containing heteroarene and features diverse substitution patterns and wide scope. The synthetic utility of our method was demonstrated by the synthesis of (−)‐phenibut and the formal synthesis of (+)‐3‐PPP and fluvirucinine A ₁ .

We describe herein an iridium-catalyzed highly diastereo- and enantioselective hydrogenation of 1,2-azaborines ac- cessing δ-aminoboronic esters of potential biological importance. This method represents the first enantioselective hydrogenation of boron-containing heteroarene and features a diverse substitution pattern and wide scope. The synthetic utility of our method was demonstrated by the synthesis of (–)-Phenibut and the formal synthesis of (+)-3-PPP and Fluvirucinine A1.